The IL-1RI co-receptor TILRR (FREM1 isoform 2) controls aberrant inflammatory responses and development of vascular disease

Summary Expression of the interleukin-1 receptor type I (IL-1RI) co-receptor Toll-like and interleukin-1 receptor regulator (TILRR) is significantly increased in blood monocytes following myocardial infarction and in the atherosclerotic plaque, whereas levels in healthy tissue are low. TILRR association with IL-1RI at these sites causes aberrant activation of inflammatory genes, which underlie progression of cardiovascular disease. The authors show that genetic deletion of TILRR or antibody blocking of TILRR function reduces development of atherosclerotic plaques. Lesions exhibit decreased levels of monocytes, with increases in collagen and smooth muscle cells, characteristic features of stable plaques. The results suggest that TILRR may constitute a rational target for site- and signal-specific inhibition of vascular disease

Heliospheric Transport of Neutron-Decay Protons

We report on new simulations of the transport of energetic protons originating from the decay of energetic neutrons produced in solar flares. Because the neutrons are fast-moving but insensitive to the solar wind magnetic field, the decay protons are produced over a wide region of space, and they should be detectable by current instruments over a broad range of longitudes for many hours after a sufficiently large gamma-ray flare. Spacecraft closer to the Sun are expected to see orders-of magnitude higher intensities than those at the Earth-Sun distance. The current solar cycle should present an excellent opportunity to observe neutron-decay protons with multiple spacecraft over different heliographic longitudes and distances from the Sun.Comment: 12 pages, 4 figures, to be published in special issue of Solar Physic

Limited Lifespan of Fragile Regions in Mammalian Evolution

An important question in genome evolution is whether there exist fragile regions (rearrangement hotspots) where chromosomal rearrangements are happening over and over again. Although nearly all recent studies supported the existence of fragile regions in mammalian genomes, the most comprehensive phylogenomic study of mammals (Ma et al. (2006) Genome Research 16, 1557-1565) raised some doubts about their existence. We demonstrate that fragile regions are subject to a "birth and death" process, implying that fragility has limited evolutionary lifespan. This finding implies that fragile regions migrate to different locations in different mammals, explaining why there exist only a few chromosomal breakpoints shared between different lineages. The birth and death of fragile regions phenomenon reinforces the hypothesis that rearrangements are promoted by matching segmental duplications and suggests putative locations of the currently active fragile regions in the human genome

Broken-Symmetry States in Quantum Hall Superlattices

We argue that broken-symmetry states with either spatially diagonal or spatially off-diagonal order are likely in the quantum Hall regime, for clean multiple quantum well (MQW) systems with small layer separations. We find that for MQW systems, unlike bilayers, charge order tends to be favored over spontaneous interlayer coherence. We estimate the size of the interlayer tunneling amplitude needed to stabilize superlattice Bloch minibands by comparing the variational energies of interlayer-coherent superlattice miniband states with those of states with charge order and states with no broken symmetries. We predict that when coherent miniband ground states are stable, strong interlayer electronic correlations will strongly enhance the growth-direction tunneling conductance and promote the possibility of Bloch oscillations.Comment: 9 pages LaTeX, 4 figures EPS, to be published in PR

IL-21/type I interferon interplay regulates neutrophil-dependent innate immune responses to Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) is a major hospital- and communityacquired pathogen, but the mechanisms underlying host-defense to MRSA remain poorly understood. Here, we investigated the role of IL-21 in this process. When administered intratracheally into wild-type mice, IL-21 induced granzymes and augmented clearance of pulmonary MRSA but not when neutrophils were depleted or a granzyme B inhibitor was added. Correspondingly, IL-21 induced MRSA killing by human peripheral blood neutrophils. Unexpectedly, however, basal MRSA clearance was also enhanced when IL-21 signaling was blocked, both in Il21r KO mice and in wild-type mice injected with IL-21R-Fc fusion-protein. This correlated with increased type I interferon and an IFN-related gene signature, and indeed antiIFNAR1 treatment diminished MRSA clearance in these animals. Moreover, we found that IFNb induced granzyme B and promoted MRSA clearance in a granzyme B-dependent fashion. These results reveal an interplay between IL-21 and type I IFN in the innate immune response to MRS

A precision six-load-component transducer: A design incorporating finite-length measurement paths

The design of an instrument is described that measures three resultant force components and three resultant moment components acting on a surface. Within the framework of linear elastostatics of an isotropic homogeneous material the device separates to a given precision the six resultant load components. Sensor paths of finite length are employed. Moreover if fiber-optic differential displacement sensors are used rather than traditional electrical resistance strain gages, the range and sensitivity of the instrument can in principle be improved without sacrificing the device stiffness. The primary reason for these improvements is that a complete solution to the equations of elasticity allows certain displacements to be measured over large distances and be combined to yield all of the resultant load components. These displacement measurements over a long distance accommodates the use of fiber-optic interferometric sensors. The use of optical sensors in contrast with electrical-resistance gages, has the potential to allow the measurement precision and range to scale with the geometry of the device rather than the maximum strain in the instrument. It becomes possible by virtue of these features to produce a better instrument.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43934/1/11340_2006_Article_BF02322149.pd

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Cichlid biogeography: comment and review

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72313/1/j.1467-2979.2004.00148.x.pd

Laser Wakefield accelerator modelling with variational neural networks

A machine learning model was created to predict the electron spectrum generated by a GeVclass laser wakefield accelerator. The model was constructed from variational convolutional neural networks which mapped the results of secondary laser and plasma diagnostics to the generated electron spectrum. An ensemble of trained networks was used to predict the electron spectrum and to provide an estimation of the uncertainty on that prediction. It is anticipated that this approach will be useful for inferring the electron spectrum prior undergoing any process which can alter or destroy the beam. In addition, the model provides insight into the scaling of electron beam properties due to stochastic fluctuations in the laser energy and plasma electron density